Effect of 6-O-sulfonate hexosamine residue on anticoagulant activity of fully O-sulfonated glycosaminoglycans

Intact and fully O[emsp4 ]-sulfonated glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, hyaluronan, heparan sulfate and heparin were chemically de-O-sulfonated on their hexosamine C-6 position (6-O[emsp4 ]-desulfonation) using N,O[emsp4 ]-bis(trimethylsilyl) acetamide. 1H NMR spectroscopy and chemical compositional analysis showed that the chemical de-O[emsp4 ]-sulfonation at C-6 position of hexosamine residues in both intact and fully O[emsp4 ]-sulfonated GAGs was completely achieved. Since GAGs and their derivatives are often used as anticoagulant agents, their anti-amidolytic activities were determined. While most of anticoagulant activity of fully O[emsp4 ]-sulfonated GAGs (FGAGs) and heparin disappeared following chemical 6-O[emsp4 ]-desulfonation, the activity of 6-O-desulfonated fully O[emsp4 ]-sulfonated dermatan sulfate (De6FDS) remained. This observation suggests the importance of the position of O-sulfonate groups for anti-coagulant activity.